Zytiga
- Generic Name: abiraterone acetate tablets
- Brand Name: Zytiga
- Drug Class: Antineoplastics, Antiandrogen
Zytiga (Abiraterone Acetate Tablets) side effects drug center
Zytiga Side Effects Center
What Is Zytiga?
Zytiga (abiraterone acetate) is is an inhibitor of CYP17 (17a-hydroxylase/C17,20-lyase) given in combination with prednisone and indicated for the treatment of patients with metastatic castration-resistant prostate cancer.
What Are Side Effects of Zytiga?
Common side effects of Zytiga include:
- joint swelling or pain
- diarrhea
- cough
- sweating
- hot flashes
- weakness
- swelling in your legs or feet
- vomiting
- high blood pressure
- shortness of breath
- urinary tract infection
- bruising
- anemia
- low blood potassium
- high blood sugar levels
- high blood cholesterol and triglycerides
Dosage for Zytiga
Zytiga is prescribed in 250 mg dosage tablets. It is important that Zytiga be taken on an empty stomach. No food should be consumed for at least two hours before the dose of Zytiga is taken and for at least one hour after the dose of Zytiga is taken.
What Drugs, Substances, or Supplements Interact with Zytiga?
Zytiga may interact with cough or cold medicines containing dextromethorphan, heart rhythm medicines, prostate or breast cancer medications, thioridazine, and antidepressants. Tell your doctor all medications and supplements you use.
Zytiga During Pregnancy and Breastfeeding
Zytiga may harm a developing fetus. Therefore, women who are pregnant or women who may become pregnant should not handle Zytiga without protection such as gloves. Patients should also be informed that it is not known whether abiraterone or its metabolites are present in semen. Patient should use a condom if having sex with a pregnant woman. The patient should use a condom and another effective method of birth control if he is having sex with a woman of child-bearing potential. These measures are required during and for one week after treatment with Zytiga.
Additional Information
Our Zytiga Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.
Zytiga Consumer Information
Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.
Call your doctor at once if you have:
- swelling in your ankles or feet, pain in your legs;
- fast or irregular heartbeats;
- a light-headed feeling, like you might pass out;
- severe headache, blurred vision, pounding in your neck or ears;
- pain or burning when you urinate;
- low red blood cells (anemia)--pale skin, tiredness, feeling light-headed or short of breath, cold hands and feet;
- low blood potassium--leg cramps, constipation, irregular heartbeats, fluttering in your chest, increased thirst or urination, numbness or tingling, muscle weakness or limp feeling;
- liver problems--stomach pain (upper right side), nausea, vomiting, dark urine, jaundice (yellowing of the skin or eyes); or
- severe low blood sugar--headache, hunger, sweating, irritability, dizziness, fast heart rate, and feeling anxious or shaky.
Common side effects may include:
- feeling very weak or tired;
- feeling very hot;
- high blood sugar;
- increased blood pressure;
- swelling in your legs or feet;
- anemia, low blood potassium;
- painful urination;
- abnormal liver function tests or other blood tests;
- joint pain or swelling;
- headache;
- nausea, vomiting, diarrhea; or
- cold symptoms such as stuffy nose, sneezing, cough, sore throat.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Read the entire detailed patient monograph for Zytiga (Abiraterone Acetate Tablets)
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Zytiga Professional Information
SIDE EFFECTS
The following are discussed in more detail in other sections of the labeling:
- Hypokalemia, Fluid Retention, and Cardiovascular Adverse Reactions due to Mineralocorticoid Excess [see WARNINGS AND PRECAUTIONS].
- Adrenocortical Insufficiency [see WARNINGS AND PRECAUTIONS].
- Hepatotoxicity [see WARNINGS AND PRECAUTIONS].
- Increased Fractures and Mortality in Combination with Radium Ra 223 Dichloride [see WARNINGS AND PRECAUTIONS].
Clinical Trial Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
Two randomized placebo–controlled, multicenter clinical trials (COU–AA–301 and COU–AA–302) enrolled patients who had metastatic CRPC in which ZYTIGA was administered orally at a dose of 1,000 mg daily in combination with prednisone 5 mg twice daily in the active treatment arms. Placebo plus prednisone 5 mg twice daily was given to patients on the control arm. A third randomized placebo–controlled, multicenter clinical trial (LATITUDE) enrolled patients who had metastatic high–risk CSPC in which ZYTIGA was administered at a dose of 1,000 mg daily in combination with prednisone 5 mg once daily. Placebos were administered to patients in the control arm. Additionally, two other randomized, placebo–controlled trials were conducted in patients with metastatic CRPC. The safety data pooled from 2230 patients in the 5 randomized controlled trials constitute the basis for the data presented in the Warnings and Precautions, Grade 1–4 adverse reactions, and Grade 1–4 laboratory abnormalities. In all trials, a gonadotropinreleasing hormone (GnRH) analog or prior orchiectomy was required in both arms.
In the pooled data, median treatment duration was 11 months (0.1, 43) for ZYTIGA–treated patients and 7.2 months (0.1, 43) for placebo–treated patients. The most common adverse reactions (≥10%) that occurred more commonly (>2%) in the ZYTIGA arm were fatigue, arthralgia, hypertension, nausea, edema, hypokalemia, hot flush, diarrhea, vomiting, upper respiratory infection, cough, and headache. The most common laboratory abnormalities (>20%) that occurred more commonly (≥2%) in the ZYTIGA arm were anemia, elevated alkaline phosphatase, hypertriglyceridemia, lymphopenia, hypercholesterolemia, hyperglycemia, and hypokalemia. Grades 3–4 adverse events were reported for 53% of patients in the ZYTIGA arm and 46% of patients in the placebo arm. Treatment discontinuation was reported in 14% of patients in the ZYTIGA arm and 13% of patients in the placebo arm. The common adverse events (≥1%) resulting in discontinuation of ZYTIGA and prednisone were hepatotoxicity and cardiac disorders.
Deaths associated with treatment–emergent adverse events were reported for 7.5% of patients in the ZYTIGA arm and 6.6% of patients in the placebo arm. Of the patients in the ZYTIGA arm, the most common cause of death was disease progression (3.3%). Other reported causes of death in ≥5 patients included pneumonia, cardio–respiratory arrest, death (no additional information), and general physical health deterioration.
COU–AA–301
Metastatic CRPC Following Chemotherapy
COU–AA–301 enrolled 1195 patients with metastatic CRPC who had received prior docetaxel chemotherapy. Patients were not eligible if AST and/or ALT ≥2.5 x ULN in the absence of liver metastases. Patients with liver metastases were excluded if AST and/or ALT >5 x ULN.
Table 1 shows adverse reactions on the ZYTIGA arm in COU–AA–301 that occurred with a ≥2% absolute increase in frequency compared to placebo or were events of special interest. The median duration of treatment with ZYTIGA with prednisone was 8 months.
Table 1:Adverse Reactions due to ZYTIGA in COU–AA–301
| System/Organ Class Adverse reaction | ZYTIGA with Prednisone | Placebo with Prednisone | ||
| (N=791) | (N=394) | |||
| All Grades1 | Grade 3–4 | All Grades | Grade 3–4 | |
| % | % | % | % | |
| Musculoskeletal and connective tissue disorders | ||||
| Joint swelling/discomfort2 | 30 | 4.2 | 23 | 4.1 |
| Muscle discomfort3 | 26 | 3.0 | 23 | 2.3 |
| General disorders | ||||
| Edema4 | 27 | 1.9 | 18 | 0.8 |
| Vascular disorders | ||||
| Hot flush | 19 | 0.3 | 17 | 0.3 |
| Hypertension | 8.5 | 1.3 | 6.9 | 0.3 |
| Gastrointestinal disorders | ||||
| Diarrhea | 18 | 0.6 | 14 | 1.3 |
| Dyspepsia | 6.1 | 0 | 3.3 | 0 |
| Infections and infestations | ||||
| Urinary tract infection | 12 | 2.1 | 7.1 | 0.5 |
| Upper respiratory tract infection | 5.4 | 0 | 2.5 | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 11 | 0 | 7.6 | 0 |
| Renal and urinary disorders | ||||
| Urinary frequency | 7.2 | 0.3 | 5.1 | 0.3 |
| Nocturia | 6.2 | 0 | 4.1 | 0 |
| Injury, poisoning and procedural complications | ||||
| Fractures5 | 5.9 | 1.4 | 2.3 | 0 |
| Cardiac disorders | ||||
| Arrhythmia6 | 7.2 | 1.1 | 4.6 | 1.0 |
| Chest pain or chest discomfort7 | 3.8 | 0.5 | 2.8 | 0 |
| Cardiac failure8 | 2.3 | 1.9 | 1.0 | 0.3 |
| 1 Adverse events graded according to CTCAE version 3.0. 2 Includes terms Arthritis, Arthralgia, Joint swelling, and Joint stiffness. 3 Includes terms Muscle spasms, Musculoskeletal pain, Myalgia, Musculoskeletal discomfort, and Musculoskeletal stiffness. 4 Includes terms Edema, Edema peripheral, Pitting edema, and Generalized edema. 5 Includes all fractures with the exception of pathological fracture. 6 Includes terms Arrhythmia, Tachycardia, Atrial fibrillation, Supraventricular tachycardia, Atrial tachycardia, Ventricular tachycardia, Atrial flutter, Bradycardia, Atrioventricular block complete, Conduction disorder, and Bradyarrhythmia. 7 Includes terms Angina pectoris, Chest pain, and Angina unstable. Myocardial infarction or ischemia occurred more commonly in the placebo arm than in the ZYTIGA arm (1.3% vs. 1.1% respectively). 8 Includes terms Cardiac failure, Cardiac failure congestive, Left ventricular dysfunction, Cardiogenic shock, Cardiomegaly, Cardiomyopathy, and Ejection fraction decreased. |
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Table 2 shows laboratory abnormalities of interest from COU–AA–301.
Table 2:Laboratory Abnormalities of Interest in COU–AA–301
| Laboratory Abnormality | ZYTIGA with Prednisone | Placebo with Prednisone | ||
| (N=791) | (N=394) | |||
| All Grades (%) |
Grade 3–4 (%) |
All Grades (%) |
Grade 3–4 (%) |
|
| Hypertriglyceridemia | 63 | 0.4 | 53 | 0 |
| High AST | 31 | 2.1 | 36 | 1.5 |
| Hypokalemia | 28 | 5.3 | 20 | 1.0 |
| Hypophosphatemia | 24 | 7.2 | 16 | 5.8 |
| High ALT | 11 | 1.4 | 10 | 0.8 |
| High Total Bilirubin | 6.6 | 0.1 | 4.6 | 0 |
COU–AA–302
Metastatic CRPC Prior to Chemotherapy
COU–AA–302 enrolled 1088 patients with metastatic CRPC who had not received prior cytotoxic chemotherapy. Patients were ineligible if AST and/or ALT ≥2.5 x ULN and patients were excluded if they had liver metastases.
Table 3 shows adverse reactions on the ZYTIGA arm in COU–AA–302 that occurred in ≥5% of patients with a ≥2% absolute increase in frequency compared to placebo. The median duration of treatment with ZYTIGA with prednisone was 13.8 months.
Table 3: Adverse Reactions in ≥5% of Patients on the ZYTIGA Arm in COU–AA–302
| System/Organ Class Adverse reaction |
ZYTIGA with Prednisone | Placebo with Prednisone | ||
| (N=542) | (N=540) | |||
| All Grades1 | Grade 3–4 | All Grades | Grade 3–4 | |
| % | % | % | % | |
| General disorders | ||||
| Fatigue | 39 | 2.2 | 34 | 1.7 |
| Edema2 | 25 | 0.4 | 21 | 1.1 |
| Pyrexia | 8.7 | 0.6 | 5.9 | 0.2 |
| Musculoskeletal and connective tissue disorders | ||||
| Joint swelling/discomfort3 | 30 | 2.0 | 25 | 2.0 |
| Groin pain | 6.6 | 0.4 | 4.1 | 0.7 |
| Gastrointestinal disorders | ||||
| Constipation | 23 | 0.4 | 19 | 0.6 |
| Diarrhea | 22 | 0.9 | 18 | 0.9 |
| Dyspepsia | 11 | 0.0 | 5.0 | 0.2 |
| Vascular disorders | ||||
| Hot flush | 22 | 0.2 | 18 | 0.0 |
| Hypertension | 22 | 3.9 | 13 | 3.0 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 17 | 0.0 | 14 | 0.2 |
| Dyspnea | 12 | 2.4 | 9.6 | 0.9 |
| Psychiatric disorders | ||||
| Insomnia | 14 | 0.2 | 11 | 0.0 |
| Injury, poisoning and procedural complications | ||||
| Contusion | 13 | 0.0 | 9.1 | 0.0 |
| Falls | 5.9 | 0.0 | 3.3 | 0.0 |
| Infections and infestations | ||||
| Upper respiratory tract infection | 13 | 0.0 | 8.0 | 0.0 |
| Nasopharyngitis | 11 | 0.0 | 8.1 | 0.0 |
| Renal and urinary disorders | ||||
| Hematuria | 10 | 1.3 | 5.6 | 0.6 |
| Skin and subcutaneous tissue disorders | ||||
| Rash | 8.1 | 0.0 | 3.7 | 0.0 |
| 1 Adverse events graded according to CTCAE version 3.0. 2 Includes terms Edema peripheral, Pitting edema, and Generalized edema. 3 Includes terms Arthritis, Arthralgia, Joint swelling, and Joint stiffness. |
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Table 4 shows laboratory abnormalities that occurred in greater than 15% of patients, and more frequently (>5%) in the ZYTIGA arm compared to placebo in COU–AA–302.
Table 4: Laboratory Abnormalities in >15% of Patients in the ZYTIGA Arm of COU–AA–302
| Laboratory Abnormality | ZYTIGA with Prednisone | Placebo with Prednisone | ||
| (N=542) | (N=540) | |||
| Grade 1–4 | Grade 3–4 | Grade 1–4 | Grade 3–4 | |
| % | % | % | % | |
| Hematology | ||||
| Lymphopenia | 38 | 8.7 | 32 | 7.4 |
| Chemistry | ||||
| Hyperglycemia1 | 57 | 6.5 | 51 | 5.2 |
| High ALT | 42 | 6.1 | 29 | 0.7 |
| High AST | 37 | 3.1 | 29 | 1.1 |
| Hypernatremia | 33 | 0.4 | 25 | 0.2 |
| Hypokalemia | 17 | 2.8 | 10 | 1.7 |
| 1 Based on non–fasting blood draws | ||||
LATITUDE
Patients with Metastatic High–risk CSPC
LATITUDE enrolled 1199 patients with newly–diagnosed metastatic, high–risk CSPC who had not received prior cytotoxic chemotherapy. Patients were ineligible if AST and/or ALT ≥2.5 x ULN or if they had liver metastases. All the patients received GnRH analogs or had prior bilateral orchiectomy during the trial. The median duration of treatment with ZYTIGA and prednisone was 24 months.
Table 5 shows adverse reactions on the ZYTIGA arm that occurred in ≥5% of patients with a ≥2% absolute increase in frequency compared to those on the placebos arm.
Table 5: Adverse Reactions in ≥5% of Patients on the ZYTIGA Arm in LATITUDE1
| System/Organ Class Adverse reaction |
ZYTIGA with Prednisone | Placebo with Prednisone | ||
| (N=597) | (N=602) | |||
| All Grades2 | Grade 3–4 | All Grades | Grade 3–4 | |
| % | % | % | % | |
| Vascular disorders | ||||
| Hypertension | 37 | 20 | 13 | 10 |
| Hot flush | 15 | 0.0 | 13 | 0.2 |
| Metabolism and nutrition disorders | ||||
| Hypokalemia | 20 | 10 | 3.7 | 1.3 |
| Investigations | ||||
| Alanine aminotransferase increased3 | 16 | 5.5 | 13 | 1.3 |
| Aspartate aminotransferase increased3 | 15 | 4.4 | 11 | 1.5 |
| Infections and infestations | ||||
| Urinary tract infection | 7.0 | 1.0 | 3.7 | 0.8 |
| Upper respiratory tract infection | 6.7 | 0.2 | 4.7 | 0.2 |
| Nervous system disorders | ||||
| Headache | 7.5 | 0.3 | 5.0 | 0.2 |
| Respiratory, Thoracic and Mediastinal Disorders | ||||
| Cough4 | 6.5 | 0.0 | 3.2 | 0 |
| 1 All patients were receiving an GnRH agonist or had undergone orchiectomy. 2 Adverse events graded according to CTCAE version 4.0 3 Reported as an adverse event or reaction 4 Including cough, productive cough, upper airway cough syndrome |
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Table 6 shows laboratory abnormalities that occurred in >15% of patients, and more frequently (>5%) in the ZYTIGA arm compared to placebos.
Table 6: Laboratory Abnormalities in >15% of Patients in the ZYTIGA Arm of LATITUDE
| Laboratory Abnormality | ZYTIGA with Prednisone | Placebo with Prednisone | ||
| (N=597) | (N=602) | |||
| Grade 1–4 | Grade 3–4 | Grade 1–4 | Grade 3–4 | |
| % | % | % | % | |
| Hematology | ||||
| Lymphopenia | 20 | 4.1 | 14 | 1.8 |
| Chemistry | ||||
| Hypokalemia | 30 | 9.6 | 6.7 | 1.3 |
| Elevated ALT | 46 | 6.4 | 45 | 1.3 |
| Elevated total bilirubin | 16 | 0.2 | 6.2 | 0.2 |
Cardiovascular Adverse Reactions
In the combined data of 5 randomized, placebo–controlled clinical studies, cardiac failure occurred more commonly in patients on the ZYTIGA arm compared to patients on the placebo arm (2.6% versus 0.9%). Grade 3–4 cardiac failure occurred in 1.3% of patients taking ZYTIGA and led to 5 treatment discontinuations and 4 deaths. Grade 3–4 cardiac failure occurred in 0.2% of patients taking placebo. There were no treatment discontinuations and two deaths due to cardiac failure in the placebo group.
In the same combined data, the majority of arrhythmias were grade 1 or 2. There was one death associated with arrhythmia and three patients with sudden death in the ZYTIGA arms and five deaths in the placebo arms. There were 7 (0.3%) deaths due to cardiorespiratory arrest in the ZYTIGA arms and 2 (0.1%) deaths in the placebo arms. Myocardial ischemia or myocardial infarction led to death in 3 patients in the placebo arms and 3 deaths in the ZYTIGA arms.
Postmarketing Experience
The following additional adverse reactions have been identified during post approval use of ZYTIGA with prednisone. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Respiratory, Thoracic and Mediastinal Disorders: non–infectious pneumonitis.
Musculoskeletal and Connective Tissue Disorders: myopathy, including rhabdomyolysis.
Hepatobiliary Disorders: fulminant hepatitis, including acute hepatic failure and death.
Cardiac Disorders: QT prolongation and Torsades de Pointes (observed in patients who developed hypokalemia or had underlying cardiovascular conditions).
Immune System Disorders - Hypersensitivity: anaphylactic reactions (severe allergic reactions that include, but are not limited to difficulty swallowing or breathing, swollen face, lips, tongue or throat, or an itchy rash (urticaria)).
DRUG INTERACTIONS
Drugs That Inhibit Or Induce CYP3A4 Enzymes
Based on in vitro data, ZYTIGA is a substrate of CYP3A4.
In a dedicated drug interaction trial, co–administration of rifampin, a strong CYP3A4 inducer, decreased exposure of abiraterone by 55%. Avoid concomitant strong CYP3A4 inducers during ZYTIGA treatment. If a strong CYP3A4 inducer must be co–administered, increase the ZYTIGA dosing frequency [see DOSAGE AND ADMINISTRATION and CLINICAL PHARMACOLOGY].
In a dedicated drug interaction trial, co–administration of ketoconazole, a strong inhibitor of CYP3A4, had no clinically meaningful effect on the pharmacokinetics of abiraterone [see CLINICAL PHARMACOLOGY].
Effects Of Abiraterone On Drug Metabolizing Enzymes
ZYTIGA is an inhibitor of the hepatic drug–metabolizing enzymes CYP2D6 and CYP2C8. In a CYP2D6 drug–drug interaction trial, the Cmax and AUC of dextromethorphan (CYP2D6 substrate) were increased 2.8–and 2.9–fold, respectively, when dextromethorphan was given with abiraterone acetate 1,000 mg daily and prednisone 5 mg twice daily. Avoid co–administration of abiraterone acetate with substrates of CYP2D6 with a narrow therapeutic index (e.g., thioridazine). If alternative treatments cannot be used, consider a dose reduction of the concomitant CYP2D6 substrate drug [see CLINICAL PHARMACOLOGY].
In a CYP2C8 drug–drug interaction trial in healthy subjects, the AUC of pioglitazone (CYP2C8 substrate) was increased by 46% when pioglitazone was given together with a single dose of 1,000 mg abiraterone acetate. Therefore, patients should be monitored closely for signs of toxicity related to a CYP2C8 substrate with a narrow therapeutic index if used concomitantly with ZYTIGA [see CLINICAL PHARMACOLOGY and WARNINGS AND PRECAUTIONS].
Read the entire FDA prescribing information for Zytiga (Abiraterone Acetate Tablets)
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